The genitourinary syndrome of menopause (GSM) is attributed to a decline in the levels of circulating sexual steroids, which often results in increased vaginal pH, atrophic urogenital changes, elevated amount of postvoid residual urine, and changes in the vaginal microbiome with a shift toward a predominance of fecal Gram-negative bacteria rather than lactobacilli, which is believed to create a potential reservoir for recurrent UTIs. Current guidelines to prevent recurrent UTIs include vaginal estrogen products. Intravaginal prasterone (dehydroepiandrosterone) is converted locally in the vaginal tissue into androgens, which are subsequently aromatized into estrogens. It is indicated to treat moderate to severe dyspareunia in postmenopausal women in the United States, and vaginal atrophy in the rest of the world. The objective of this study was to assess, through real-world evidence data, the potential of vaginal prasterone to be used in postmenopausal women with GSM with recurrent UTIs as prophylaxis to reduce the future UTI risk. As a sensitivity analysis, women using aromatase inhibitors, medications that stop the production of estrogen in postmenopausal women typically prescribed to women with a history of breast cancer, were analyzed. This sensitivity analysis is particularly interesting since these patients are only metabolizing prasterone into androgens, and not estrogens. It should be noted that the use of intravaginal prasterone is not contraindicated in patients with a history of breast cancer in the United States and Canada.

This retrospective matched-cohort study was conducted using the Integrated Dataverse (IDV), an open-source claims database from Symphony Health Solutions, with data from February 2015 through January 2020. The IDV database includes claims for both medical and pharmacy services from deterministically linked data from 3 sources: pharmacy point of service; payer adjudication services (clearing houses); and direct pharmacy, medical, and hospital feeds. Data are de-identified and comply with the requirements of the Health Insurance Portability and Accountability Act.

Cohorts of women with GSM treated with vaginal prasterone and women with GSM not receiving any GSM treatment were created. A total of 22,245 women treated with prasterone for a minimum of 12 weeks were matched to women without any prescribed GSM-related treatment. Two hundred eighty-six women with GSM taking aromatase inhibitors and treated with vaginal prasterone were matched 1:1 to women with GSM taking aromatase inhibitors, but not taking any prescribed GSM-related treatment. Across all age groups, women treated with prasterone have a significantly lower UTI prevalence compared to those untreated (6.58% and 12.3%, respectively; P < .0001). The highest difference in UTI prevalence among the prasterone treated and untreated women was observed in those aged 65-74 (7.15% and 16.2%, respectively; P < .0001). Consistent with the above, among aromatase inhibitor users, women treated with prasterone have a significantly lower UTI prevalence (4.90% vs 9.79%; P = .008).

This study suggests that intravaginal prasterone may be a good candidate for prophylaxis in postmenopausal women with recurrent UTIs to reduce future UTI risk, including for patients taking aromatase inhibitors and having contraindications for estrogen-based therapies. This study is, however, based on real-world evidence and warrants further investigation in a prospective clinical setting.